Pharmaceutical compositions



United States Patent No Drawing. Filed May 15, 1958, Ser. No. 735,358

6 Claims. (Cl. 167-55) --This invention is concerned with new and valuable pharmaceutical compositions and with a process for enhancing the valuable action of certain known medicinal agents. In particular, this invention is concerned with compositions of salicylates, which are effective therapeutic agents, and glucosamine or non-toxic salts of glucosamine.

The salicylates, such as aspirin, have been known for many years as highly valuable agents for inducing analgesia or for dulling painful reactions of the animal system including that of humans. They are also of value for alleviating the pain ofvarious conditions, such as rheumatism, arthritis, neuralgia, and in rheumatic fever and so forth. The salicylates are used in a variety of forms, such as acetylsalicylic acid (aspirin), sodium salicylate, ammonium salicylate, and various chemically related compounds which have comparable activity, such as gentisic acid salts, salicylamide. and sodium y-resorcylate. These valuable compounds are usually rapidly absorbed into the system upon oral administration and exert their valuable efiect with a fair degree of rapidity.

It has now been found that the valuable properties of the salicylate-type therapeutic agents referred to above may be appreciably enhanced by use of the compositions and process of the present invention. The compositions of the present invention comprise a salicylate therapeutic agent, such as aspirin, sodium salicylate, or one of the other related compounds, or mixtures of these, together with at least one compound of the group glucosamine, non-toxic glucosamine salts, and compounds which are readily hydrolyzed to glucosamine under conditions prevailing during the use of the compositions. Various nontoxic inorganic or organic salts of glucosamine, particularly water soluble salts such as the hydrochloride, sulfate, phosphate, acetate, citrate, tartrate, gluconate, malate, succinate, and so forth, may be used in these compositions. Rather than administering a composition of the two types of material, the individual materials may be administered separately and in either order. The valuable eifect is obtained as long as the time interval between administration of the two dilferent components is not too great. In general the interval should not be greater than about 30 minutes although this will vary somewhat depending on the size and weight of the patient and the particular dosage form used, e.g. tablet, capsule, solution, etc.

The valuable effect which is obtained by the use of the present compositions and process is a definite enhancement of the level of salicylate in the blood stream. The valuable effect is obviously of considerable assistance where rapid and efiective therapeuatic results are desired. For instance, in the treatment of rheumatic fever, it may be particularly desirable to obtain the maximum blood level of salicylate which is possible without causing any undesirable toxic reaction. Through administration of a composition of any one of the salicylate-type agents, together with a suitable quantity of glucosamine or a suitable derivative thereof, or the coadministration of the two individual agents, there is obtained a definitely higher and more effective blood level of the salicylate than can be obtained through use of the salicylate alone in the same quantity. It should be noted that, if it is desired, a mixture of 'difierent types of tice.

, 3,008,874 Patented Nov. 14, 1961 salicylates, such as a mixture of sodium salicylateand aspirin, may be used. Furthermore, a mixture of different types of the glucosamine agents may be used; for instance, a mixture of glucosamine and glucosamine hydrochloride is suitable.

In general, a preferred proportion of the glucosaminetype compound (calculated as free glucosamine) is from about one-quarter to about two times the weight of the salicylate-type compound. Although lesser or greater proportions may be used, there is no particular advantage to such a change.

In general, the enhanced activity of the compositions of the present invention are apparent on oral administration. A variety of diiferent types of oral compositions may be used for this purpose. Thus, the materials may be incorporated into tablets, troches, lozenges, aqueous solutions, or suspensions, solutions or suspensions in non-aqueous vehicles and other orally administrable preparations such as are commonly used in medical prac- These may be prepared with the usual flavoring agents, sweetening agents, coloring agents, and, in.the case of tablets, binders, tablet lubricants and other suitable excipients. These materials should, of course, be chosen so as not to interfere in any way with the absorption of the salicylate or with the enhancing action of the glucosamine-type compound. The dosage of salicylates for treatment of various types of conditions, which are susceptible to salicylate therapy, is well known in medical practice. No substantial deviation from such dosage levels is used when these materials are administered with the glucosamine-type compounds. If desired, the amount of salicylate used for treating a given condition may be reduced with the resulting effectiveness equal to that of the higher level of salicylate alone. In some conditions, where very high levels of salicylate are used, the present compositions permit a reduction of the dosage to avoid toxic effects of such high levels without any reduction in the therapeutic effect.

The following examples are given by way of illustration and are not to be considered as the sole embodiments of this invention. It is to be understood that protection hereof is only limited by the specific wording of the appended claims.

Example 1 Time Aspirin Aspirin plus Glucosamine 15 Min 1.05 1.27 30 Min--- 1.92 2. 86 60 Min.-- 3.22 3. 120 Min 3. 93 4. l5

In each case the value reported is the salicylate level in the blood serum in terms of milligrams per cc. It is apparent from the table that there is a definite and highly useful enhancement of the salicylate blood level effected by the use of a composition of aspirin with glucosamine.

Example 2 Hard gelatin capsules containing one gram of sodium salicylate and 0.25 gram of glucosamine hydrochloride 3 are administered to a group of adult human patients. Determination of the blood level indicates a definite enhancement of salicylate absorption. Repetition of the experiment with 0.5 gram of sodium salicylate and 1 gram of glucosarnine gives comparable results.

What is claimed is:

1. An orally administrable therapeutic composition which comprises a salicylate therapeutic agent and a glucosamine compound chosen from the group consisting of glucosamine and non-toxic salts thereof.

2. A therapeutic composition which comprises from about one-quarter to about two parts by weight of a compound chosen from/the group consisting of glucosamine and non-toxic salts of glucosamine and one part by Weight of a non-toxic salicylate.

3. A process for obtaining enhanced salicylate therapy which comprises orally administering a salicylate therapeutic agent to a patient, and substantially concurrently administering a compound chosen from the group consisting of glucosamine and non-toxic salts of glucosamine.

4. A process for obtaining enhanced salicylate therapy which comprises orally administering aspirin to a patient and substantially concurrently administering g'lucosamine.

5. A process for. obtaining enhanced salicylate therapy which comprises orally administering sodium salicylate to a patient and substantially concurrently administering glucosamine hydrochloride.

6. A process for obtaining enhanced salicylate therapy which comprises orally administering sodium salicylate to a patient and substantially concurrently administering glucosamine.

References Cited in the file of this patent UNITED STATES PATENTS Miller et a1 Dec. 14, 1937 Miller et a1 Apr. 1 9, 1938 OTHER REFERENCES Perosa et al.: J.S.M.A., vol. 160, No. 6, February 11, 1956, p. 514.

Jenkins et al.: Chemistry of Organic Medicinal Products, 4th ed., 1957, John Wiley and Sons, New York, pp. 234/235.

Journal of the Amer. Pharmaceutical Association, Practical Pharmacy Ed., March 1958, pp. and 171.

D.T.N., November 3, 1958, p. 65, Manufacturing Section.

Kent et al.: Biochemistry of the Aminosugars, Academic Press, Inc., publ., New York (1955)., pp. 26-27 and 133. 

3. A PROCESS FOR OBTAINING ENHANCED SALICYLATE THERAPY WHICH COMPRISES ORALLY ADMINISTERING A SALICYLATE THERAPEUTIC AGENT TO A PATIENT, AND SUBSTANTIALLY CONCURRENTLY ADMINISTERING A COMPOUND CHOSEN FROM THE GROUP CONSISTING OF GLUCOSAMINE AND NON-TOXIC SALTS OF GLUCOSAMINE. 